"Normal aging" may be an oxymoron. In fact, `theories` on why mammals "age", meaning experience progressive decline in physiologic function compared with that expected for "young", but "mature" adults of the same species, are numerous. While theories abound, there is no generally recognized theory of aging, nor is there any recognized therapy to "retard the normal aging process".
Caloric restriction may be the most widely accepted means to retard `normal aging` (Schneider, E., and J. Reed. Modulations of Aging Processes. Perspectives on Aging and Mortality. Handbook of the Biology of Aging. 2nd ed. 1985. van Nostrand, Rineholt Co., N.Y. pp.45-76) and (Raloff, J. Searching out how a severe diet slows aging. Science News. Oct. 5, 1991, p. 215). As first described by McCay, he noted that laboratory rats, fed a nutritionally adequate but calorically deficient diet, had longer mean and maximum life expectancies than control rats (McCay, C., Crowell, M., and L. Maynard; The effect of retarded growth upon the length of life span and upon the ultimate body size. J. Nutrition. 10: 1935, pp.63-79). Since chronic caloric restriction also results in retarded growth, and is otherwise impractical, caloric restriction has largely remained a laboratory model.
Other current `theories of aging` include the `free radical` or `oxidative damage` hypothesis (Orr, W., and R. Sohal. Extension of Life-Span by Overexpression of Superoxide Dismutase and Catalase in Drosophila melanogaster. Science. 263: Feb. 25, 1994, pp. 1128-1130) and (Floyd, R. Oxidative Damage to Behavior During Aging. Science. 254: Dec. 13, 1991, p. 1597). Free radicals are small molecules, either oxygen free radicals or hydroperoxides that have an unpaired electron. These chemical species are extremely reactive and cause substantial damage to biomolecules such as proteins, DNA, RNA, and lipids. The resulting accumulative damage is thought to be associated with the declining physiologic functions considered `aging`. This theory has been directly demonstrated using the life span in mutant fruit flies (Orr, W., and R. Sohal. Extension of Life-Span by Overexpression of Superoxide Dismutase and Catalase in Drosophila melanogaster. Science. 263: Feb. 25, 1994, pp.1128-1130).
Selegiline is a selective monoamine oxidase-B (MAO-B) inhibitor, which is widely used as an adjunct in the treatment of Parkinson's disease. While its most common usage is for the treatment of Parkinson's disease, selegiline was originally developed as an antidepressant agent. Recent testing has indicated that selegiline may have some effect on increasing sexual response in aging animals, and also may have some effect, at least in rats, in increasing the natural life expectancy. However, to date selegiline has only been medically approved by regulatory agencies for use for treatment of Parkinson's disease.
The search for new lines of medication to improve the quality of life in senescence ever continues. This becomes especially important in modern-day society, especially in developed countries, where the proportion of citizens over 65 years of age continues to increase. In sum, the quality of life has become increasingly important in older years, as people continue to experience longer life expectancy.
There is, therefore, a continuing and real need for the development of medications which retard the normal deterioration of certain physiological functions.
It is a primary objective of the present invention to develop a dosage regimen for the use of selegiline to shift the survival curve for a longer lived mammal such as pet dogs, cats or horses. (`Life span` is the inate or inborn maximal biologic life of a species, whereas `life expectancy` is the predicted actual life or average life of a species. Rarely is the `life expectancy` as long or equivalent to the biologic `life span` of a species.) While selegiline is a known compound that has been used to extend the life expectancy of laboratory rodents (Knoll, J., Dallo, J. and T. T. Yen. Striatal Dopamine, Sexual Activity and Lifespan. Longevity of Rats Treated With (--)Deprenyl. Life Sciences. Vol. 45, no. 6. 1989. pp.525-531), (Milgram, N. W., et al. Maintenance on L-Deprenyl Prolongs Life In Aged Male Rats. Life Sciences. Vol. 47, no. 6. 1990. pp.415-420), (Kitani, K., et al. Chronic Treatment of (--)Deprenyl Prolongs The Life Span of Male Fischer 344 Rats. Further Evidence. Life Sciences. Vol. 52, no. 3. 1993. pp.281-288), there is no prior teaching that would allow extrapolation from a short lived species, such as laboratory rats, to the relatively longer lived species such as dogs, cats, horses or even humans.
Like most drugs, selegiline can have diverse physiological effects which are completely dependent upon the dose administered. In accordance with the present invention, selegiline can be used for successful methods of treatment to provide the desired physiological effects enumerated herein, providing that it is used at the dosage levels mentioned herein, and providing it is administered at the periodic intervals and for the time spans mentioned herein. Obviously, when different dosages and levels of treatment are used, the results expressed herein may not be achieved. In fact, at higher doses adverse behavioral effects may be encountered.